Vitamin E and the Vitamin E and the Risk of Prostate Risk of Prostate

CancerCancer

Vitamin E and the Vitamin E and the Risk of Prostate Risk of Prostate

CancerCancerThe Selenium and Vitamin E Cancer The Selenium and Vitamin E Cancer

Prevention Trial (SELECT)Prevention Trial (SELECT)The Selenium and Vitamin E Cancer The Selenium and Vitamin E Cancer

Prevention Trial (SELECT)Prevention Trial (SELECT)

Klein, Thompson, Tangen, et al. J Amer Med Assoc, Oct 12, 2011; Vol 306, Klein, Thompson, Tangen, et al. J Amer Med Assoc, Oct 12, 2011; Vol 306, No.14; 1549 - 1556No.14; 1549 - 1556

Zachary LapaquetteZachary LapaquettePharmD CandidatePharmD Candidate

University of GeorgiaUniversity of Georgia

Background

16% of men will be diagnosed with prostate cancer in their lifetime1

Most common type of cancer in U.S. men, other than non-melanoma skin cancer2

Second leading cause of cancer-related death in U.S. men

BackgroundBackground

Vitamin E is fat-soluble and has anti-oxidative properties

Recommended daily allowance for vitamin E is 22.4IU (15mg) daily3

Doses of 50IU/day were shown to decrease prostate cancer incidence in smokers4

SELECT TrialSELECT Trial

Randomized, placebo-controlled, multi-center trial

Compared selenium 200mcg/day, vitamin E 400IU/day, or both against placebo

Planned follow-up minimum of 7 years and maximum of 12 years

Inclusion CriteriaInclusion CriteriaHealthy

Age 50 or older for African Americans, or 55 for all other men

No h/o prostate cancer diagnosis

PSA < 4ng/mL

Normal DRE

No current use of anticoagulants

No h/o hemorrhagic stroke

Normal blood pressure

MethodsMethodsParticipants without prostate cancer had clinic visits every 6 months; with prostate cancer, annually

Annual PSA and DRE were not mandatory

Prostate cancer status was determined by self-report at each 6-month visit

Pathology report, tissue then sent to SELECT

MethodsMethods

Study was blinded until 10/23/2008, when participants discontinued use of study agents

Non-blinded follow-up occurred until 07/2011

Statistical AnalysisStatistical Analysis

Primary end point: Prostate cancer incidence as determined by routine clinical management

Other areas of study: colorectal cancer, lung cancer, all other primary cancers, deaths (all cause), development of diabetes, CVE

1- and 2-sided P values given

Statistical AnalysisStatistical Analysis

Proportional hazards model used

Unlike linear regression, proportional hazards models do not assume normal distribution and allow for censored data

Men without end-point of interest were censored at last contact date

Chi-squared test used to test the difference in the relative risk of diabetes

ResultsResults

Total of 35,533 men randomized at 427 centers into placebo (n=7594 had final follow-up data), vitamin E (n=7650), selenium (n=7626), selenium +vitamin E (n=7620)

No significant differences in age, race, baseline PSA, or diagnostic testing

ResultsResultsPlacebo

(n=8696)Vitamin E (n=8737)

Selenium (n=8752)

Vitamin E + Selenium (n=8702)

No. of prostate cancers

529 620 575 555

Hazard ratio (99% CI)

1.17 (1.004-1.36)

1.09 (0.93-1.27) 1.05 (0.89-1.22)

P value 0.008 0.18 0.46

Absolute Risk

9.3 10.9 10.1 9.7

Gleason >7, No. 133 155 161 164

Hazard Ratio (99% CI)

1.16 (0.86-1.58) 1.21 (0.9-1.63) 1.23 (0.91-1.66)

P value 0.20 0.11 0.08

ResultsResultsPlacebo

(n=8696)Vitamin E (n=8737)

Selenium (n=8752)

Vitamin E + Selenium (n=8702)

All cancers 1108 1190 1132 1149

Hazard ratio (99% CI)

1.07 (0.96-1.19) 1.02 (0.92-1.14 1.02 (0.92-1.14

P value 0.13 0.59 0.60

Diabetes 869 918 913 875

Relative risk (99% CI)

1.05 (0.93-1.17) 1.04 (0.93-1.17) 0.99 (0.89-1.12)

P value 0.29 0.34 0.91

Authors’ CommentAuthors’ Comment

An explanation for the increased risk of prostate cancer in the vitamin E arm is not apparent

The insignificant increased risk in the vitamin E + selenium arm implies that selenium may have a protective effect

This study is seems to contradict ATBC and PHS II studies

Caution should be used when recommending or studying high doses of micronutrients

Health effects from these agents may continue even after the intervention is stopped

ConclusionConclusion

Healthy men with average risk of prostate cancer subjected to contemporary community standards of screening and biopsy who took a common dose of vitamin E have a significantly increased risk of prostate cancer.

The increased risk implies that seemingly innocuous yet biologically active substances such as vitamins can cause harm

Consumers need be skeptical of health claims for unregulated over-the-counter products in the absence of strong evidence of benefit

Presenter’s Comment

Presenter’s Comment

Study has good reach, but is limited to healthy men 50+ years old

Criticism of study:

Did not have best- and worst-case censure analysis

Data collection dependent on self-report

427 research sites

Overall strong study

Placebo event rate: 529/8696 = 0.0608

Presenter’s Comment

Presenter’s Comment

NNH = 98

Vit E prostate cancer rate: 620/8737 = 0.0710

Placebo prostate cancer rate: 529/8696 = 0.0608

Works CitedWorks Cited

1.Klein, Thompson, Tangen, et al. Vitamin E and the Risk of Prostate Cancer: The Selenium and Vitamin E Cancer Prevention Trial. J Amer Med Assoc, Oct 12, 2011; Vol 306, No.14; 1549 - 1556

2.National Cancer Institute. “A Snapshot of Prostate Cancer.” Sep 2010 <http://www.cancer.gov/aboutnci/servingpeople/snapshots/prostate.pdf>

3.National Institutes of Health. “Dietary Supplement Fact Sheet: Vitamin E.” Oct 2011 <http://ods.od.nih.gov/factsheets/VITAMINE>

4.Heinonen et al. Prostate cancer and supplementation with alpha-tocopherol and beta-carotene: incidence and mortality in a controlled trial. J Natl Cancer Inst. 1998 Mar 18;90(6):440-6.